The purpose of this K23 career development proposal is to obtain additional resources, protected time, and training so that I can become an independent, patient-oriented researcher, focusing on C. difficile-associated disease (CDAD) and infections in hematopoietic stem cell transplant (HSCT) recipients. I am in the process of obtaining a Masters of Science in Public Health and I am taking courses in epidemiology, ethical conduct of research, and advanced statistical analysis. I have a mentor, Dr. Victoria Fraser, who is an expert in the field of nosocomial infection outcomes and prevention and a faculty advisory committee to facilitate my research and career development. CDAD is the most common cause of nosocomial, infectious diarrhea and causes increased morbidity, length of stay, and costs. HSCT recipients have many risk factors for CDAD and are extremely immunosuppressed. They are at high risk for developing CDAD and severe CDAD. However, there are few studies of CDAD in this patient population, and the studies published are limited by small sample sizes and inadequate study design. The Specific Aims of the research proposal are to: 1) Determine the risk factors and clinical outcomes of CDAD following allogeneic HSCT, specifically whether granulocyte colony stimulating factor (GCSF) reduces the risk of CDAD and the relationship between CDAD and subsequent development of graft vs. host disease (GVHD). To achieve this aim I will perform a 3-year prospective longitudinal cohort study of allogeneic HSCT recipients. 2) Determine how donor immunity to C. difficile and changes in HSCT recipient serum levels of C. difficile anti-toxin antibodies influence risk and outcomes of CDAD in allogeneic HSCT recipients. 3) Determine the transmission dynamics of C. difficile on a HSCT unit by prospectively culturing patients, the environment and health care workers'hands for C. difficile. Multivariate analysis will be performed to evaluate the relative impact of asymptomatically colonized patients, environmental contamination and health care workers'hands as drivers of CDAD acquisition and transmission. RELEVANCE (See instructions): Clostridium difficile is a healthcare-associated, antibiotic resistant pathogen of increasing importance in the US and abroad. The proposed research will contribute to our knowledge of the pathogenesis and transmission of Clostridium difficile in stem cell transplant recipients and the general population.